DIAGNOSIS; Dizzying Symptoms

By LISA SANDERS, M.D.

Published: June 6, 2010

''I feel a swimming in my head,'' mumbled the voice on the phone. Dr. Stephanie Pouch, a resident in her second year of training, wasn't sure what to make of this elderly gentleman's strange complaint. Was he feeling dizzy? He wasn't sure; all he could say was that his head was ''swimming'' and that he almost passed out. Uncertain of the cause or even the nature of the complaint, Pouch sent the man to the emergency room. She was on call that day at the University of Chicago Medical Center. She would figure it out when he got there.

Once Pouch found the 68-year-old man in the busy emergency department, a quick glance at his chart explained his vague complaint: his blood pressure was so low it could barely be measured. Whenever he tried to stand, his blood pressure dropped even further, and his head began to swim. A look at the patient himself explained the dangerously low blood pressure: he was severely dehydrated. His eyes were dull and apathetic; his dark skin hung off the bones of his face as if it were a size too large. Beneath a graying, well-trimmed mustache, his lips were dry and cracked, and he passed an equally dry tongue across them frequently.

He was started on intravenous fluids. That would certainly help. But what happened to bring him to this state? The patient was a man of few words. But slowly, with the help of the patient's wife, Pouch was able to put together his story. For the past several months the patient was plagued by severe diarrhea. He was in the bathroom 5 to 10 times a day. And the pattern repeated itself at night. He couldn't remember the last time he had an uninterrupted night's sleep. He had no pain, no fever or chills, just these endless trips to the bathroom.

As the patient spoke, Pouch's eyes were drawn to his hands. They were covered by strange stripes of dark, thick, rough skin that started at the knuckles and extended all the way down the fingers. She gently turned one of the patient's hands to look at the palm and found more of the same. He had the rash a long time, he told her, for weeks, maybe months. Pouch found the same rash on his back, chest and feet.

The rash was like nothing Pouch had seen before. Still, it was the diarrhea -- not the rash -- that brought the patient to the hospital. She forced herself to focus on the problem: what could be causing this persistent and profuse diarrhea? Pouch paged through the patient's thick chart. He had a lot of medical problems: diabetes, atherosclerotic disease (also known as hardening of the arteries) and, usually, high blood pressure. This combination of diseases could cause diarrhea by limiting the amount of blood that reaches the intestines and starving the tissue. There were many other possible causes of severe diarrhea: infection was one; cancer another. Certain tumors can cause diarrhea by producing too much digestive hormone.

Pouch sent off samples of the patient's stool to look for evidence of infection and blood for overproduction of hormones. The patient also needed an ultrasound of the blood vessels that feed the gut to see if blood flow was compromised.

The next morning on rounds, Pouch presented the patient to the attending physician, Dr. Vineet Arora. The more experienced Arora was worried about the patient's prolific diarrhea, but she was also struck by the unusual rash. Could they be part of the same disease process? Patients like this man are the most difficult to assess, Arora later told me, because they have many medical problems, and it's difficult to distinguish the foreground (the disease) from the background (the complicated and sometimes abnormal base-line state that now represents the patient's normal condition).

There were some important diseases to consider that could cause diarrhea and a rash. Celiac disease -- a sensitivity to a component of wheat known as gluten -- can cause both. And the rash in celiac disease, unlike most rashes, can spread to the palms of the hands and soles of the feet. Zinc deficiency could cause both. So could a number of B vitamin deficiencies. Pouch quickly ordered a series of blood tests for these deficiencies.

Over the next several days, the patient improved significantly. His diarrhea slowed, his blood pressure rose and he could sit and stand without the dizziness that took him to the hospital. Meanwhile, test results dribbled in but provided no real answers. The ultrasound confirmed the hardening of the arteries but showed adequate blood flow to his intestines. There was no evidence of infection. He didn't have celiac disease. It wasn't zinc deficiency. After nearly a week, the patient was better and was sent home, though the team still didn't know what made him sick.

A couple of days later, Arora and her team got their answer -- or at least part of it. The blood tests they ordered revealed that the patient had a severe deficiency of vitamin B6. Initially, Arora was flummoxed. Vitamin B6 deficiency is rare in this country, and while it can cause pain in the hands and feet, it causes neither a rash nor diarrhea. Finally, she hit pay dirt: deficiencies of this essential nutrient caused the patient to develop a condition known as pellagra. First described by 18th-century European physicians, the name pellagra comes from an Italian description of its most common symptoms: the ''rough skin'' that Arora and Pouch were first struck by when examining this patient.

For centuries, the disease was thought to be caused by an infection, but we now know that pellagra comes from a deficiency of niacin. If an individual is not ingesting niacin, the body can create it, but it needs vitamin B6 to do so. In medical school we are taught that pellagra is characterized by the four Ds: diarrhea, dermatitis (rash), dementia and death. This patient had two of the four.

If this vitamin B6 deficiency explained the rash and diarrhea, what explained the vitamin B6 deficiency? Again, Arora wasn't sure. Further reading led to the answer. The patient was taking hydralazine, a blood-pressure medication that had the side effect of eliminating vitamin B6 from the body. Hydralazine was an old blood-pressure medication that slipped from use as newer, easier-to-take medications were developed. But a few years ago a study suggested that hydralazine might be particularly useful in African-Americans. This new information brought the old medication to the current generation of doctors -- and African-American patients like this one. That hydralazine can also cause a vitamin deficiency was common knowledge in this medication's first life but seems to have been forgotten in its reprise.

Now the story was beginning to make sense: the hydralazine caused the vitamin-B6 deficiency, which, in turn, led to the niacin deficiency and pellagra. The patient's diarrhea caused the low blood pressure. While he was in the hospital, the doctors were not giving him hydralazine because his blood pressure was low. Without the hydralazine the patient was able to absorb vitamin B6 and make niacin. By the time he was discharged, the diarrhea had improved strikingly. Arora contacted Dr. Kevin Thomas, the patient's primary-care physician, who immediately started him on vitamin B6 supplements. The diarrhea resolved completely within a week; the remarkable rash disappeared over the next two weeks.

Arora and Pouch presented this case to other doctors and found that few of them were aware of this side effect of hydralazine. ''Why don't we know this anymore?'' Arora asked me, amazed. ''If this medicine is going to be used again, then doctors definitely need to know about this problem.''

DRAWINGS (DRAWING BY DAN WINTERS); GRAPHICS: ODD RASH: Dark, rough skin started at the knuckles and extended all the way down the fingers.; DIARRHEA: The patient was in the bathroom 5 to 10 times during the day.; BLOOD PRESSURE: Readings were very low, but he usually suffered from the opposite problem. (MM26); A deficiency of niacin, above, or zinc can cause diarrhea and a rash. (MM28) (DRAWING BY DAN WINTERS)